8-Chloro-2-Methyl-1,5-naphthyridine synthesis

Yield: 67%

Reaction Conditions:

Stage #1:6-methyl-[1,5]naphthyridin-4-ol with trichlorophosphate for 2 h;Heating / reflux;
Stage #2: with ammonia in water

Steps:

20
8-Chloro-2-methyl-[1,5]naphthyridine; The suspension of 6-methyl-[1,5]naphthyridin-4-ol (1.60 g, 9.99 mmol) in POCl₃ (25 mL) was heated under refluxing for 2 hrs. After cooling to room temperature, the reaction mixture was quenched with ice water and basified with NH₄OH followed by extraction with AcOEt. The organic layer was washed with brine and dried over NaSO4, and concentrated to give 8-chloro-2-methyl-[1,5]naphthyridine as a brown solid (1.2 g, 67%). HR-MS-EI (+) m/e calcd for C₉H₇N₂Cl (M+) 178.0298, found 178.0297.

References:

Location in patent:Page/Page column 9; 19